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Review
. 2025 Sep 2;17(9):e91510.
doi: 10.7759/cureus.91510. eCollection 2025 Sep.

Challenges and Opportunities of Early Parkinson's Disease Biomarkers: α-Synuclein, Leucine-Rich Repeat Kinase 2 (LRRK2), DJ-1, and microRNAs

Allie Heineman  1 , Jillian Linck  2 , Adi Eylon  3 , Mayur S Parmar  4
Affiliations
Review

Challenges and Opportunities of Early Parkinson's Disease Biomarkers: α-Synuclein, Leucine-Rich Repeat Kinase 2 (LRRK2), DJ-1, and microRNAs

Allie Heineman et al. Cureus. .

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss, leading to motor symptoms (tremor, rigidity, bradykinesia, postural instability) and non-motor symptoms (autonomic dysfunction, cognitive dysfunction, olfactory dysfunction, mood disorders such as depression). Pathologically, PD involves Lewy bodies, aggregates of phosphorylated α-synuclein (α-Syn) driven by genetic or environmental factors. α-Syn, detectable in cerebrospinal fluid (CSF), blood, and saliva, is a promising biomarker for early diagnosis and monitoring. Other candidates, including leucine-rich repeat kinase 2 (LRRK2), DJ-1, and microRNAs (miRNAs), reflect genetic, oxidative stress, and gene regulatory changes in PD. Ideal biomarkers should be sensitive, specific, non-invasive, and track disease progression. However, PD's heterogeneity, biofluid variability (e.g., hemolysis), methodological inconsistencies, and the need for large-scale validation pose challenges. Standardization of sample collection, assays, and cohort characterization is critical for clinical application. This review evaluates α-Syn, LRRK2, DJ-1, and miRNAs, highlighting their strengths, limitations, and potential. Advanced assays targeting specific α-Syn species, LRRK2 kinase activity, oxidized DJ-1, and miRNA panels, alongside non-invasive matrices (saliva, skin, retina) and multi-biomarker approaches, offer significant opportunities for early detection and therapy monitoring, warranting further research and standardization.

Keywords: alpha-synuclein; dj-1; lrrk2; micrornas (mirnas); parkinson-plus syndromes; parkinson’s disease (pd); serum biomarker.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

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